Trial reportCell reports. Medicine2023
Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes.
Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph
Trial report in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02384889 (Targeting Polyamines Using DFMO in Persons With Type 1 Diabetes), which is not on this map. Cited by 19 papers.
0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
7.9field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Targeting Polyamines Using DFMO in Persons With Type 1 Diabetes: A Randomized, Double-Masked, Placebo-Controlled Phase I Study to Evaluate the Safety, Tolerability, and Initial Pharmacodynamics of Multiple Ascending Doses
Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- New and emerging therapies in type 1 diabetes mellitus.The Journal of clinical investigation · 2026Review
- Macrophage-intrinsic and IL-9-dependent arginine metabolism promotes lung tumor growth.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Podocyte Metabolic Reprogramming and Targeted Therapy.Journal of the American Society of Nephrology : JASN · 2026Review
- Using animal models to decipher the role of polyamines in the pancreas and β Cell.Amino acids · 2026Review
- The functional roles and mechanisms of polyamines in age-related bone diseases.Cellular and molecular life sciences : CMLS · 2025Review
- Islet-intrinsic sex differences in inflammatory signaling contribute to autoimmune diabetes susceptibility.bioRxiv : the preprint server for biology · 2025Article
- Autoimmune Type 1 Diabetes in the Era of Disease-Modifying Immune Therapy.Diabetes/metabolism research and reviews · 2025Review
- Development of chemokine network inhibitors using combinatorial saturation mutagenesis.Communications biology · 2025Article
- SCFA biotherapy delays diabetes in humanized gnotobiotic mice by remodeling mucosal homeostasis and metabolome.Nature communications · 2025Article
- Design, Synthesis, and Biological Activity of Novel Ornithine Decarboxylase (ODC) Inhibitors.Journal of medicinal chemistry · 2025Article
- Metabolic interventions as adjunctive therapies to insulin in type 1 diabetes: Current clinical landscape and perspectives.Diabetes, obesity & metabolism · 2025Review
- Polyamine biosynthesis dysregulation in Alzheimer's disease and Down syndrome cellular models.bioRxiv : the preprint server for biology · 2025Article
- Polyamines mediate cellular energetics and lipid metabolism through mitochondrial respiration to facilitate virus replication.PLoS pathogens · 2024Article
- Secreted GDF15 maintains transcriptional responses during DNA damage-mediated senescence in human beta cells.American journal of physiology. Endocrinology and metabolism · 2024Article
- Increased hepatic putrescine levels as a new potential factor related to the progression of metabolic dysfunction-associated steatotic liver disease.The Journal of pathology · 2024Article
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Unveiling the hidden players: noncoding RNAs orchestrating polyamine metabolism in disease.Cell & bioscience · 2024Review
- Discordant Effects of Polyamine Depletion by DENSpm and DFMO on β-cell Cytokine Stress and Diabetes Outcomes in Mice.Endocrinology · 2024Article
- Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors.International journal of molecular sciences · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 10 institutions in 1 country.
Emily K SimsDivision of Pediatric Endocrinology and Diabetology, Herman B. Wells Center for Pediatric Research, Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: eksims@iu.edu.
Abhishek KulkarniKovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Audrey HullDivision of Pediatric Endocrinology and Diabetology, Herman B. Wells Center for Pediatric Research, Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Nationwide Children's Hospital Pediatric Residency Program, Columbus, OH 43205, USA.
Stephanie E WoernerDivision of Pediatric Endocrinology and Diabetology, Herman B. Wells Center for Pediatric Research, Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Susanne CabreraDepartment of Pediatrics, Section of Endocrinology and Diabetes, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Lucy D MastrandreaDivision of Pediatric Endocrinology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA.
Batoul HammoudDepartment of Pediatrics, The University of Chicago, Chicago, IL 60637, USA.
Soumyadeep SarkarBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
Ernesto S NakayasuBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
Teresa L MastracciDepartment of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Susan M PerkinsDepartment of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Fangqian OuyangDepartment of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Bobbie-Jo Webb-RobertsonBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
Jacob R EnriquezKovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Sarah A TerseyKovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Carmella Evans-MolinaDivision of Pediatric Endocrinology and Diabetology, Herman B. Wells Center for Pediatric Research, Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Medicine and the Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Roudebush VA Medical Center, Indianapolis, IN 46202, USA.
S Alice LongBenaroya Research Institute, Center for Translational Immunology, Seattle, WA 98101, USA.
Lori BlanchfieldBenaroya Research Institute, Center for Translational Immunology, Seattle, WA 98101, USA.
Eugene W GernerCancer Prevention Pharmaceuticals, Tucson, AZ 85718, USA.
Raghavendra G MirmiraKovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, IL 60637, USA; Department of Pediatrics, The University of Chicago, Chicago, IL 60637, USA. Electronic address: mirmira@uchicago.edu.
Linda A DiMeglioDivision of Pediatric Endocrinology and Diabetology, Herman B. Wells Center for Pediatric Research, Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Indiana University School of MedicineUniversity of Chicago · USPacific Northwest National Laboratory · USBenaroya Research InstituteCancer Prevention Pharmaceuticals (United States) · USMedical College of Wisconsin · USNationwide Children's Hospital · USRichard L. Roudebush VA Medical Center · USUniversity at Buffalo, State University of New York · USUniversity of Indianapolis · US
Funding
Quality Assurance and Quality Control Project Management: Improving Submissions and Study Conduct in the Human Subjects Research Prior Approval ProcessUL1TR002529 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI MOE, SHARON M, WIEHE, SARAH ELIZABETH · 2018 to 2022
$27.2MPilot and Feasibility ProgramP30DK020595 · NIDDK · UNIVERSITY OF CHICAGO · PI Raghavendra G Mirmira · 2013 to 2026
$20.9MIntegrated Islet Distribution Program (U24) - 2021U24DK098085 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Carmella Evans-Molina, Joyce Carol Niland · 2021 to 2026
$17.8MTranslation CoreP30DK097512 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Carmella Evans-Molina · 2015 to 2026
$17.4MTranscriptional Mechanisms Governing Beta Cell DifferentiationR01DK060581 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Raghavendra G Mirmira · 2002 to 2026
$8.5MThe Integrated Stress Response in Human Islets During Early T1DU01DK127786 · NIDDK · UNIVERSITY OF CHICAGO · PI EVANS-MOLINA, CARMELLA, MIRMIRA, RAGHAVENDRA G · 2020 to 2025
$7.1MRole of Polyamines and Hypusine in Nutrient-Induced Beta-Cell Growth and ReplicationR01DK124906 · NIDDK · UNIVERSITY OF CHICAGO · PI Raghavendra G Mirmira · 2020 to 2026
$4.0MImplications of Changes in Islet Exosomal Cargo in Type 1 DiabetesR01DK133881 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI EVANS-MOLINA, CARMELLA, MIRMIRA, RAGHAVENDRA G · 2022 to 2025
$2.7MControl of beta cell function and survival by RYR2-mediated calcium signalsR01DK127236 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI EVANS-MOLINA, CARMELLA · 2021 to 2025
$2.2MImmunoengineering Postdoctoral Training Program - Resubmission - 1T32AI153020 · NIAID · UNIVERSITY OF CHICAGO · PI ALEGRE, MARIA-LUISA, SWARTZ, MELODY ANN · 2021 to 2025
$2.1MBeta cell extracellular vesicles in health and diseaseR01DK121929 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI SIMS, EMILY K · 2020 to 2024
$2.0MExocrine-Endocrine Crosstalk and Determinants of Beta Cell GrowthR01DK121987 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI MASTRACCI, TERESA LOUISE · 2020 to 2024
$2.0MBLRD VA I01 BX001733NCATS NIH HHS UL1 TR002529NIAID NIH HHS T32 AI153020NIDDK NIH HHS P30 DK020595NIDDK NIH HHS P30 DK097512NIDDK NIH HHS R01 DK060581NIDDK NIH HHS R01 DK121929NIDDK NIH HHS R01 DK121987NIDDK NIH HHS R01 DK124906NIDDK NIH HHS R01 DK127236NIDDK NIH HHS R01 DK127308NIDDK NIH HHS R01 DK133881NIDDK NIH HHS U01 DK127786NIDDK NIH HHS U24 DK098085
Abstract
In preclinical models, α-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, delays the onset of type 1 diabetes (T1D) by reducing β cell stress. However, the mechanism of DFMO action and its human tolerability remain unclear. In this study, we show that mice with β cell ODC deletion are protected against toxin-induced diabetes, suggesting a cell-autonomous role of ODC during β cell stress. In a randomized controlled trial (ClinicalTrials.gov: NCT02384889) involving 41 recent-onset T1D subjects (3:1 drug:placebo) over a 3-month treatment period with a 3-month follow-up, DFMO (125-1,000 mg/m
Indexed as
Diabetes Mellitus, Type 1AnimalsEflornithineHumansMiceOrnithine DecarboxylaseOrnithine Decarboxylase InhibitorsPutrescineEflornithineOrnithine DecarboxylaseOrnithine Decarboxylase InhibitorsPutrescinedisease modificationisletornithine decarboxylasepolyaminespreventiontrialtype 1 diabetesα-difluoromethylornithineβ cellβ cell stress
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390
Registered trials
NCT02384889ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.